Regulation of insulin-stimulated tyrosine phosphorylation of Shc and IRS-1 in the muscle of rats: effect of growth hormone and epinephrine.
Insulin receptor substrate-1 (IRS-1) and Shc protein have the same binding site at the insulin receptor and compete in their association with the phosphorylated receptor. The present study demonstrates that a decrease in the level of muscle insulin receptor phosphorylation induced by chronic growth hormone (GH) treatment or acute epinephrine infusion is accompanied by a reduction in the level of IRS-1 phosphorylation and in the association with phosphatidylinositol 3-kinase. In contrast, no change is observed in insulin-stimulated Shc tyrosine phosphorylation, or in the association of this substrate with Grb2. These data suggest that a reduction in insulin receptor phosphorylation may affect post-receptor processes differentially by preserving the phosphorylation of some substrates and pathways, but not of others.
Thirone
A C
AC
Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, S.P., Brazil.
Paez-Espinosa
E V
EV
Carvalho
C R
CR
Saad
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D006614:Hindlimb; D019382:Human Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000378:metabolism*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D019382:Human Growth Hormone; D014443:Tyrosine; D004837:Epinephrine